BRI’s Matt Dufort, PhD, and Peter Linsley, PhD, led two new studies that could help doctors predict how quickly type 1 diabetes (T1D) will progress in some people, and match them with treatments that could slow it down.

“T1D moves much faster in some people than in others, and that increases their risk of long-term problems like heart disease and stroke,” Dr. Dufort says. “Our discoveries could help fast progressors get the right treatment early on. It means they could stay healthier, and it’s a step toward tailored treatments that could improve the lives of many more people with T1D.”

Pinpointing Fast Progressors

People with T1D who are fast progressors stop making insulin – a hormone that regulates blood sugar – relatively quickly, and often at a young age. Making even a little bit of natural insulin can prevent or delay some of T1D’s long-term complications.

Dr. Dufort and his colleagues – including Peter Linsley, PhD, Carla Greenbaum, MD, Alice Long, PhD, and Cate Speake, PhD – set out to look for differences between fast progressors and patients whose T1D develops more slowly.

The researchers found that young fast progressors (under age 20) had increased numbers of B cells, a type of white blood cell, in their blood. Dufort and his colleagues built on this discovery by finding that an immunotherapy drug called rituximab can hinder T1D’s progress in these patients by blocking B cells.

“Now we’ll work to confirm these results, and then we can hopefully move toward using a test that detects whether young T1D patients have higher B cell levels,” Dr. Speake says. “Based on those results, doctors could someday prescribe rituximab to try to slow T1D’s progression in younger patients.”

Closer to Tailored Treatments

The BRI researchers made two other findings that could enable precision medicine for more T1D patients.

Dufort and his colleagues described a new way to predict how quickly T1D will progress in any T1D patient: measuring a protein fragment called C-peptide that plays a key role in insulin production.

“This could forecast how far along a patient’s T1D will be in two years, so doctors can eventually prescribe treatment based on that prognosis,” Dr. Dufort says. Dr. Linsley led a related study that investigated how another immunotherapy drug, called abatacept, affects T1D patients.

Dr. Linsley’s study showed that patients who don’t respond to the drug produce more B cells.

“If patients start taking abatacept and their doctor sees elevated B cells, they could adjust their dosage of abatacept or switch to a different treatment,” Dr. Linsley says.

Launching a Clinical Trial

 These projects were funded by JDRF and NIH, and are fueling a new clinical trial that combines rituximab and abatacept for T1D.

“No one has tested these two drugs together in T1D, and we’re interested in whether this can prevent or delay the disease,” Dr. Speake says.

“It’s not enough to understand why the immune system becomes imbalanced in diseases like T1D,” Dr. Greenbaum says. “We also have to find ways to rebalance the immune system so we can improve people’s lives, and our collaborations help us do that as quickly as possible.”

Fighting Diseases

June 20, 2019

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